The objective of the proposed research is to investigate the mechanism of action of thyroid hormones at the cellular level through a study of the relationship between hormone-receptor interactions, hormone actions and hormone metabolism. This study will be carried out on the anuran amphibian, Xenopus laevis during various stages in its development, as it acquires sensitivity to thyroid hormones and later undergoes metamorphosis into an adult frog in response to the action of these hormones. This research will concentrate on the mechanism of action of thyroid hormones on tadpole tail and liver tissues. The actions of thyroid hormones will be studied both in vivo during spontaneous metamorphosis and in isolated tail and liver tissues cultured in vitro in the presence of thyroid hormones. The proposed research will be concerned with: 1. Determining the molecular mechanism underlying acquisition of sensitivity to thyroid hormones. This study will examine the relationship between the acquisition of sensitivity to thyroid hormones, the ability of a tissue to metabolize the hormones, and the appearance of specific binding sites for the hormones. 2. Elucidating the molecular nature of thyroid hormone- target cell interactions. This will incude an investigation into the existence of specific, saturable receptors for thyroid hormones in responsive target cells. If specific receptors are found to exist, then their intracellular location and biochemical characteristics will be examined.